The chromatography technique is widely used in different forms for separating chemical and biological substances and there are many applications in compound preparation, purification and analysis. Liquid chromatography is of particular importance in the pharmaceutical and biological industries for the preparation, purification and analysis of proteins, peptides and nucleic acids.
A typical liquid chromatography apparatus has an upright housing in which a bed of packing material, which is usually particulate in nature and consists of a porous medium, rests against a permeable retaining layer. A liquid mobile phase enters through an inlet, for example at the end of an adaptor rod which has an elongated extension within the column. The liquid mobile phase thereafter enters a distributor plate which distributes the liquid mobile phase through a porous, perforated filter, mesh, frit or net, which together with the distributor plate is arranged on an adaptor. The liquid mobile phase thereafter moves through the bed of packing material and is finally removed via an outlet, typically through a second filter, mesh, frit or net and a second distributor plate.
Columns used in liquid chromatography typically comprise a tubular body enclosing the porous chromatography medium through which the carrier liquid or mobile phase flows, with separation of substances or analytes taking place between the mobile phase and solid phase of the porous medium. Typically, the porous medium is enclosed in the column as a packed bed, generally formed by consolidating a suspension of discrete particles, known as slurry that is pumped or poured into the column when the uppermost, first end unit and the adaptor assembly have been removed. The production of a stable, even bed is often critical to the final separation process.
Conventional distribution systems for use in liquid chromatography comprise a distributor plate attached to the net. The distributor plate comprises channels arranged in a pattern to substantially uniform distribute the fluid over the plate. The distributor plate is perforated with holes or openings which lead the fluid from the channels and uniformly into the packed bed.
During the chromatography process the packed bed may be damaged and fines may occur in the column. After several chromatography cycles the fines may clog the net or nets in the column, which may result in higher back pressure and lower process efficiency. Therefore, maintenance of the chromatography columns must be conducted frequently and the nets or filters must be replaced after a number of cycles.
The backing plate or the lowermost, second end unit of the chromatography columns generally acts as a support for the column, being itself supported on legs or some other base arrangement positioned on the floor which allows clearance for outlet pipe work projecting beneath the column.
When such a column should be packed with a packing material and/or requires maintenance to, or cleaning of, internal components, such as the valves, seals, meshes/screens/filters, distribution systems etc., heavy lifting gear such as a crane or hoist is necessary to lift the uppermost, first end unit and the adaptor assembly away from the column tube and also the column tube away from the lowermost, second end unit as these assemblies can have e considerably weigh. The use of heavy overhead lifting equipment to disassemble the column in order to carry out internal maintenance is not desirable. Operator safety is obviously a concern when heavy equipment is lifted overhead and technicians exposed below. Furthermore, alignment structures are required to keep the column and its base/adaptor assemblies axially aligned as they are separated from each other, to avoid damage to the precision components.
The presence of such alignment and lifting structures imposes significant obstructions around the tube and need to be carefully laid out to provide sufficient clearance at some point of the circumference for insertion/removal of the internal components. Furthermore, the requirement to use heavy lifting equipment imposes constraints on housing such columns, sufficient overhead space and support being required to accommodate hoists or cranes. As many chromatography columns are now run in “clean” environments under GMP, to avoid microbiological contamination, where it is extremely difficult to accommodate overhead equipment, the requirement of moving the column to another room for disassembly, maintenance and/or packing is problematic. This problem is exacerbated by the need to clean and verify the column before re-turning it for use to the clean environment. The presence of hoists or cranes in GMP facilities used for biopharmaceutical manufacturing is thus highly undesirable for the above mentioned reasons, together with the fact that these machines shed particulate matter, in the form of dirt, during their operation and maintenance.
Document US 2004/0164012 A1 discloses a chromatography column that removes the longitudinal load from the column tube altogether and transfer it to a yoke and stanchion arrangement situated around but external to the column tube. By using the yoke and stanchion sys-tem a central adjuster can be used to move the top and end into and out of the housing. When internal pressure is applied to the column, the tube experiences no longitudinal load. The yoke and stanchion allow for complete removal of the end from the tube and provides a place to retain the end while the tube is being filed emptied, cleaned or repaired.
However, the chromatography column in US 2004/0164012 A1 has significant disadvantages associated with it by virtue of its design. As can be seen from US 2004/0164012 A1 the end is always connected to the yoke and the rest of the column and may therefore not be handled on separate places. Also, in order to remove the end from the interior of the column, the operator must lift the yoke and the end part to the retained state. As industrial columns typically have diameters ranging from about 200 mm to 2000 millimeters, this means that heavy lifts sometimes have to be performed. Therefore, maintenance and packing of the column disclosed in US 2004/0164012 A1 may thus be complicated and imposes a significant safety risk for the operator.
There are known chromatography columns provided with welded or heat shrinked nets on the distributor plate, which distributor plate in turn is removably connected by fastening elements on the adaptor. Time and cost consuming operations are necessary in order to remove the clogged net from the distributor plate. Especially, when the chromatography column is of a large size the removal of the net from the distributor plate by using milling or turning machines is complicated. The replaced net must be welded or heat shrinked on the distributor plate before remounting on the adaptor. The chromatography column may not be used under a substantially period of time during the replacement of the nets. This may lead to production losses in the pharmaceutical and biological industries.
Notwithstanding the existence of such prior art chromatography columns, there is a need to improve the maintenance and packing methods available for chromatography columns by providing columns which are safer and easier for operators to use. Also, there is a need to reduce cost and time when conducting maintenance on and packing of chromatography columns. Also, there is a need to reduce complexity and to reduce needed floor space when conducting maintenance on and packing of chromatography columns.